The seeds of fenugreek(Trigonella foenumgraecum L.), which have a long history for use in traditional Chinese medicine, are reported to possess some hypocholesterolemic effect. To clarify the mechanism for cholesterol-lowering action, effects of fenugreek on the function and mRNA expression of intestinal cholesterol transporters, Niemann-Pick C1-Like 1(NPC1L1)and ATP binding cassette(ABC)transporters: ABCA1, ABCG5, and ABCG8, were examined in Caco-2 cells. Fenugreek seed water extract significantly inhibited both the net transport of cholesterol from the apical to basolateral side and the accumulation into the cells. Significant suppression in mRNA expression of the cholesterol transporters NPC1L1, ABCA1, ABCG5, ABCG8 and the transcription factor liver X receptor was observed in the cells treated with fenugreek. These results suggest that fenugreek possibly has inhibitory effectson mRNA expression and transport activity of the active cholesterol transporters, leading to the decreased net absorption of cholesterol from the intestine.